The primary purpose of the Organic Synthesis Facility (OSF) is to produce the highest quality synthetic molecules for Fox Chase Cancer Center (FCCC) investigators. The OSF was used by 19 investigators with peer-reviewed funding in calendar year 2009. Over eighty-five percent (85.4%) of use was in support of peer-reviewed, funded investigators in calendar year 2009. Small organic molecules are used in many areas of research as specific reagents including those that are inhibitors of enzyme activity or protein binding. Some of these molecules have been used in the development of prodrugs against target proteins identified at FCCC. Analogues of natural substrates have been used to probe enzyme mechanism, to investigate protein function, or to lest specific hypotheses. The molecules synthesized by the Facility are not purchasable from chemical companies, and custom synthesis from commercial enterprises is either not available or prohibitively expensive. The demand for synthetic services and especially the demand for novel compound synthesis have increased significantly over this current funding period. In order to meet this need, the efficiency and productivity of the Facility have been increased with the addition of a seasoned Ph.D. chemist to the staff and by acquisition of a new LC-MS system. In addition to increasing efficiency, the LC-MS system provides the Facility with new capabilities and services. During the last grant period (calendar years 2006-2009), 79 different chemical syntheses were completed including 44 novel compounds for 17 investigators in four Research Programs. The compounds synthesized were very diverse in structure and included a series of tamoxifen analogues, drug-conjugated antibodies, p53 inhibitors, Paki inhibitors, and photosensitizers. The OSF provided analytical, purification and consulting services to 46 investigators from all five Research Programs and seven Shared Facilities during the current funding period. In the last four calendar years (2006-2009), the average number of requests for these analytical and purification services was 59 per month, compared to 34 in calendar years 2000-2004. The large user group of 46 investigators from all five Research Programs and seven Shared Facilities indicates that the materials produced and services provided by the Facility are necessary for the scientific objectives of a wide range of research projects being carried out throughout the Center.